The hypothesis to be tested in the present program project grant is whether more exact correction of blood sugar concentrations in the diabetic pregnancy, particularly in the first trimester, will increase fetal salvage, decrease fetal congenital malformations, and decrease neonatal morbidity and mortality. Characterization of insulin receptors and insulinase activity in purified placental membrane preparations, and calcium transport of placental organelles, examination of amniotic fluid metabolic indices, C peptide insulin and glucagon, fetal echocardiographic examination of cardiac function and anatomy, and examination of maternal and neonatal vitamin D, parathyroid hormone, calcitonin and photon absorptiometric analyses of bone mineralization will be utilized to assess the results of strict blood sugar control. A chronically catheterized sheep model will evaluate the effects of maternal hyperglycemia, ketoacidosis and uterine hypoperfusion, and the effects of fetal polycythemia on fetal and neonatal cardiovascular and renal function. These studies will allow a basic understanding of the physiology and pathophysiology involved in the diabetic pregnancy, and permit a rational approach for decreasing fetal and neonatal deaths and morbidity in the offspring of the diabetic pregnancy.